Cutaneous melanoma is a lethal skin tumor with continuously rising incidence, resulting in a growing healthcare burden [1, 2]. Worldwide, roughly 232,000 new cases and 55,000 deaths were reported in 2012 [3]. Patients diagnosed with localized disease have a five-year survival rate of more than 95% after treatment by surgical excision alone [4]. If the cancer is more advanced, however, survival rates drop substantially, i.e., 30% to 60% after five years, primarily depending on the tumor thickness, i.e., Breslow's depth.
Metastatic disease generally leads to poor patient outcomes, as treatment options were limited for a long time. However, rapid development of next-generation sequencing technologies has identified most genetic alterations and molecular pathways involved in melanoma development and provided the basis for novel targeted therapies [5]. Moreover, novel immunomodulatory therapies are successfully being developed for melanoma treatment [6].
Currently, the American Joint Committee on Cancer (AJCC) classifies patients predominantly based on histological features of the primary tumor, i.e., Breslow thickness, ulceration, and mitotic rate, and indicates that the initial biopsy is a critical component of both diagnosis and staging [7]. In addition, the presence of advanced disease stage (stage III/IV) and, to a lesser extent, patient age, gender, and tumor location, are prognostic melanoma factors. Breslow thickness is viewed as the most important prognostic parameter, however, 20-30% of patients diagnosed with thin melanomas (<2.0 mm thickness) still die from their disease [8, 9]. Hence, improvements to the current staging system that lead to more accurate prediction of prognosis are warranted, allowing clinicians to better address prognosis of individual patients. Moreover, it is of importance to identify high-risk patients with aggressive disease at an early stage as these patients may benefit from more extensive surgery, adjuvant therapy, and closer follow-up.
In summary, cutaneous melanoma is a highly aggressive skin cancer that accounts for approximately 75% of skin cancer-related deaths. Despite an increased understanding of the biology of melanoma development and the identification of molecular alterations that accompany melanoma progression [10, 30], the AJCC melanoma staging and classification system has not yet incorporated potential molecular changes [7]. However, improvements to the current staging system are necessary to more accurately identify individual patients with aggressive disease at diagnosis. These patients with a so-called poor prognosis might benefit from additional therapy leading to improved clinical management and better patient outcome.